用于剖析BCL-2家族相互作用组的光反应性环肽BH3
Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome.
作者信息
Braun Craig R, Mintseris Julian, Gavathiotis Evripidis, Bird Gregory H, Gygi Steven P, Walensky Loren D
机构信息
Department of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Chem Biol. 2010 Dec 22;17(12):1325-33. doi: 10.1016/j.chembiol.2010.09.015.
Abstract
Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design.
摘要
定义蛋白质相互作用是发现生物途径、疾病机制以及治疗干预机会的基础。为了利用结构化肽的强大结合亲和力和选择性来进行相互作用组发现，我们设计了光反应性的钉状BH3肽螺旋，它们能共价捕获其生理性BCL-2家族靶点。交联的α螺旋能共价捕获静态和动态的蛋白质相互作用体，并能快速识别相互作用位点，为相互作用组发现和靶向药物设计之间提供了关键联系。
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